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Biodistribution and Pharmacokinetic Studies of a Porphyrin Dimer Photosensitizer (Oxdime) by Fluorescence Imaging and Spectroscopy in Mice Bearing Xenograft Tumors

Authors

  • Mamta Khurana,

    Corresponding author
    1. Department of Medical Biophysics, University of Toronto/Ontario Cancer Institute, Toronto, ON
      Corresponding author email: mamta.khurana@gmail.com (Mamta Khurana); harry.anderson@chem.ox.ac.uk (Harry Anderson); wilson@uhnresearch.ca (Brian Wilson)
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  • Sébastien Ulrich,

    1. Chemistry Research Laboratory, Department of Chemistry, Oxford University, Oxford OX1 3TA, UK
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  • Anthony Kim,

    1. Department of Medical Biophysics, University of Toronto/Ontario Cancer Institute, Toronto, ON
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  • Yumi Moriyama,

    1. Department of Medical Biophysics, University of Toronto/Ontario Cancer Institute, Toronto, ON
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  • George Netchev,

    1. Department of Medical Biophysics, University of Toronto/Ontario Cancer Institute, Toronto, ON
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  • Margarete K. Akens,

    1. Sunnybrook Research Institute, University of Toronto, Toronto, ON
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  • Harry L. Anderson,

    Corresponding author
    1. Chemistry Research Laboratory, Department of Chemistry, Oxford University, Oxford OX1 3TA, UK
      Corresponding author email: mamta.khurana@gmail.com (Mamta Khurana); harry.anderson@chem.ox.ac.uk (Harry Anderson); wilson@uhnresearch.ca (Brian Wilson)
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  • Brian C. Wilson

    Corresponding author
    1. Department of Medical Biophysics, University of Toronto/Ontario Cancer Institute, Toronto, ON
      Corresponding author email: mamta.khurana@gmail.com (Mamta Khurana); harry.anderson@chem.ox.ac.uk (Harry Anderson); wilson@uhnresearch.ca (Brian Wilson)
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Corresponding author email: mamta.khurana@gmail.com (Mamta Khurana); harry.anderson@chem.ox.ac.uk (Harry Anderson); wilson@uhnresearch.ca (Brian Wilson)

Abstract

Herein, we present a study of the pharmacokinetics and biodistribution of a butadiyne-linked conjugated porphyrin dimer (Oxdime) designed to have high near-infrared (NIR) 2-photon absorption cross-section for photodynamic therapy (PDT). Changes in biodistribution over time were monitored in mice carrying B16-F10 melanoma xenografts, following intravenous injection. Using fluorescence imaging of live animals and analyzing isolated organs ex vivo at different time points between 30 min and 24 h after injection, accumulation of Oxdime was measured in several organs (heart, kidney and liver) and in tumor. The concentration in the plasma was about 5–10 times higher than in other tissues. The fluorescence signal peaked at 3–12 h after injection in most tissues, including the tumor and the plasma. The change in the fluorescence emission spectrum of the sensitizer over time was also monitored and a shift in the maximum from 800 to 740 nm was observed over 24 h, showing that the Oxdime is metabolized. Significant quantities accumulated in the tumor, indicating that this PDT sensitizer may be promising for cancer treatment.

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